Lesions in DNA often pose considerable impediments to genome duplication. To overcome this block to DNA replication, cells utilize specialized accessory factors that allow synthesis of nascent DNA chains opposite the blocking lesion. Recent studies suggest that many of the key participants in Translesion DNA synthesis are phylogenetically related DNA polymerases that have collectively been termed the Y-family of DNA polymerases. In the past year, scientific studies within the section have focussed on understanding the molecular mechanisms of translesion replication in all three kingdoms of life: bacteria, archaea and eukaryotic cells. In E. coli, this process only occurs when UmuC physically interacts with UmuD' to form UmuD'2C, (polV). Because polV is a low-fidelity enzyme, its activities within the cell are strictly controlled at the transcriptional level as well as at multiple post-translational steps. Indeed, recent studies suggest that the ability of polV to facilitate translesion replication is greatly attenuated in the presence of UmuD (the mutagenically inactive precursor to UmuD'). Although UmuD' can homodimerize with itself as well as form a heterotrimeric complex with UmuC, it preferentially heterodimerizes with UmuD. As a consequence, UmuC is displaced from the polV complex, causing it to aggregate as an inactive insoluble precipitate. Scientist within the section previously identified and cloned a DinB homolog from the archaeon Sulfolobus solfataricus P2, called DNA polymerase IV (Dpo4). Characterization of the enzyme reveals that the protein possesses many biochemical properties similar to eukaryotic members of the Y-family polymerases including a propensity to bypass certain DNA lesions like a thymine-thymine cyclobutane pyrimidine dimer. S. solfataricus Dpo4 has recently been crystallized and ternary complexes of the polymerase together with a cyclobutane pyrimidine dimer and an incoming nucleotide have been solved by X-ray crystallography. These structures reveal that the active site of the enzyme is sufficiently large enough to accommodate the covalently linked pyrimidine dimer and the structural studies provide a model as to how eukaryotic polymerases, like pol eta, can efficiently and accurately bypass a pyrimidine dimer. Studies with murine DNA polymerase iota revealed that it possesses enzymatic properties similar to human pol iota in that it exhibits a remarkable template-dependent misincorporation spectrum on undamaged DNA in vitro. During attempts to make a targeted disruption of murine pol iota, scientist within the section serendipitously discovered that the commonly used 129 strain of mice carries a single nucleotide polymorphism in the Poli gene which changes the Serine 27 codon to an amber stop codon and abrogates synthesis of the polymerase. Because pol iota is an extremely error prone polymerase, it has been hypothesized to participate in somatic hypermutation of immunoglobulin variable genes. Analysis of somatic hypermutation in the pol iota-deficient 129 mice revealed, however, that they exhibit normal levels of mutagenesis and a normal mutation spectrum. Thus, it appears that either pol iota does not participate in somatic hypermutation or that its role is non-essential and has been assumed by another low-fidelity DNA polymerase.